The candidate is a surgical pathologist whose immediate research goals are the detection and molecular characterization of circulating tumor cells (CTC) and micrometastases in solid tumors, especially prostatic carcinoma (PC). His long term goals are the 1) development of these molecular tests into clinically relevant prognostic markers and 2) an in depth analysis of the mechanisms of metastases in solid tumors. Memorial Sloan Kettering Cancer Center has the clinical and laboratory facilities appropriate for the training of junior faculty members and the conduct of this type of research. The objectives of this proposal are to assess the prognostic significance of CTC in metastatic PC (MPC) and characterize these cells for alterations in markers of tumor progression. CTC will be detected in the peripheral blood of 300 men with MPC using reverse transcriptase (RT) polymerase chain reaction (PCR) for prostate specific antigen (PSA), prostate specific membrane antigen (PSMA) and prostate tumor inducing gene (PTI-1) mRNAs. We will study the variation in PSA, PSMA and PTI-1 PCR results in relation to serial sampling, diurnal variation and digital rectal examination of the prostate. The CTC will be captured using the immunobead filtration technique and analyzed at the immunohistochemical level for alterations in the expression of the E-cadherin/catenin adhesion complex and the metastasis suppressor gene KAI-1. The molecular data will be correlated with survival and other clinico-pathologic parameters. This will increase our understanding of the metastatic process in PC, and provide new prognostic markers aimed at better stratifying and therefore more accurately treat PC patients.